By Markham Heid
In the United States, most of the public’s interest has been focused on the progress of the various vaccine candidates that could provide the ultimate form of protection against the novel coronavirus.
Much less attention has been paid to monoclonal antibodies, which are drugs that contain specialised proteins meant to stop SARS-CoV-2 from infecting healthy cells. In many ways, these drugs do the work of a vaccine, only that they do it more quickly and efficiently – if also less durably.
“Antibody-based therapies may offer one of the best near-term options for developing safe, effective treatments for Covid-19,” Francis Collins, MD, PhD, director of the National Institute of Health, said in May. Since then, research teams have isolated monoclonal antibodies that – in test tubes and in monkeys – have blocked SARS-CoV-2 from spreading.
Experts say that, in a best-case scenario, monoclonal antibodies could act as a “bridge” drug to carry us safely forward until that time when a vaccine is available for wide dissemination. And they say that best-case scenario is not far-fetched.
Vaccines versus monoclonal antibodies
Human blood contains hundreds of thousands of different antibodies. Antibodies are proteins made by the immune system that can attack or repel viruses and other pathogens (disease-causing organisms).
In oversimplified terms, vaccines work in part by encouraging the immune system to make new antibodies – ones that are able to defeat a particular pathogen.
Once the immune system starts to make these antibodies, it doesn’t stop. And so, unless a virus mutates in a way that renders those antibody proteins ineffective, anyone who possesses them is protected from that virus.
Monoclonal antibody treatments are, basically, an infusion of these same virus-repelling proteins. The idea is that, once inside the body, they’ll circulate widely in the blood and neutralise the offending pathogen. But because the immune system isn’t making them, they stop working after a while.
“They generally last about a month, but you can modify them to last as long as six months,” says Myron Cohen, MD, a distinguished professor and director of the Institute for Global Health & Infectious Diseases at the University of North Carolina School of Medicine.
Cohen is helping to lead the monoclonal-antibody arm of a US government-led Covid-19 research network. He says that the monoclonal antibodies now in trials are ones that have been isolated from the blood of Covid-19 survivors.
Cohen points out that these drugs can’t offer the same level of protection as a vaccine but vaccines can, in some cases, require several doses and several months before they become effective. With monoclonal antibody drugs, the helpful proteins are likely to work almost immediately – albeit temporarily.
“Conceptually, monoclonal antibodies make sense – we’re essentially giving sick people the antibodies they need to fight the infection,” John Swartzberg, MD, clinical professor emeritus of infectious diseases and vaccinology at the University of California, Berkeley School of Public Health.
He adds: “What is making all of this very difficult to predict is that we don’t know what part of our immune system correlates with protection from SARS-CoV-2.”
Swartzberg explains that antibodies are not always the immune system’s primary weapon. In many cases, specialised immune cells – not antibodies – are needed to stop an infection.
“If the cell-mediated immune response turns out to be critical, monoclonal antibodies may not play much of a role,” he says. It’s also possible that a large variety of antibodies – not just one or two – are required to knock out SARS-CoV-2. That’s something a vaccine could provide but which monoclonal antibody therapies likely cannot.
Cohen agrees that there are a lot of challenges and unanswered questions. He says that monoclonal antibodies have been around for two decades, but they’re typically used to treat diseases in which the body’s inflammatory processes are doing damage.
“For infectious agents, we don’t have a lot of experience with them,” he says. Also, because of the way Covid-19 progresses in the body, monoclonal antibodies may be most helpful during the early stages of the disease or as an immunity booster; they may be less helpful as a treatment for advanced Covid-19 cases.
“The solution to the Covid-19 pandemic is not just monoclonal antibodies. For that, you need a vaccine,” Cohen says. However, until a vaccine is ready, doctors could give monoclonal antibodies to newly infected people in the same way that they currently give antibiotics to those who have a bacterial infection.
“Once a person has Covid-19 symptoms, they could go to their doctor and get the monoclonal antibody treatment, which is how we treat most infections today,” he says, adding: “It would mean that we might be done with ICUs and hospitalisations.”
Monoclonal antibodies could also be administered for protection in some high-risk groups – such as older adults in nursing homes or people who live with someone who has Covid-19. “It would be protection-as-needed until a vaccine is ready,” he says.
Knowing if the antibodies work
At least two different private drug companies – Eli Lilly and Company and Regeneron Pharmaceuticals, Inc. – are now conducting human clinical trials on monoclonal antibodies. Cohen says several more research efforts aren’t far behind.
“It is possible, and probably even likely, that monoclonal antibody trials will give us answers more quickly than vaccine trials,” he says, adding that those answers may come as soon as September or October.
As is the case among vaccine developers, some of the companies exploring monoclonal antibodies are already producing tens of thousands of doses of these treatments. If these work, they could quickly turn the tide in the world’s war against the coronavirus.
A lot remains to be seen. But along with vaccines and antiviral drugs, monoclonal antibodies are another promising area of research that could help the world escape from the pandemic’s grasp.
- An Elemental dispatch. Markham Heid is a health and science writer.